NULL HYPOTHESIS

In patients with mild, persistent asthma, continuous, daily treatment for 18 months with: (1) inhaled and oral placebos, (2) an inhaled corticosteroid, or (3) an oral leukotriene antagonist do not differ in their effects on airflow obstruction, as reflected by the change in AM PEF.

DESIGN

Inclusion criteria included physician-diagnosed asthma, age 18-65 years, and FEV₁ > 70% of predicted, with either > 12% and ł 200 ml improvement following albuterol inhalation or bronchial hyperreactivity (methacholine PC₂₀ < 16 mg/ml). Patients were randomized to one of three treatment arms: (1) budesonide (200 µg bid); (2) oral zafirlukast (20 mg bid); (3) placebo (“intermittent-only” treatment). All were instructed to take open-label budesonide or prednisone as guided by the symptom-based action plan. The run-in and treatment phases both ended with a 14-day period of intense combined therapy, called PICT (prednisone 0.5 mg/kg/d, budesonide 800 mg 2x/d, and zafirlukast 20 mg 2x/d) and acute treatment with albuterol (540-720 mg). The primary outcome was AM peak expiratory flow (PEF). Other outcomes included pre- and post-bronchodilator FEV₁, exacerbation frequency, asthma control, symptom-free days, and quality of life.

RESULTS

Enrollment for IMPACT began in May 2000 and the last patient visits occurred in May 2003. There were 225 randomized patients (73 on budesonide, 76 on zafirlukast, and 76 on placebo). The three groups yielded similar increases in AM PEF (7-9%, ~32 L/min; p = 0.90) and similar rates of asthma exacerbation (14/73 on budesonide, 6/76 on zafirlukast, and 10/76 on placebo, p = 0.238), even though the intermittent-only group took budesonide for an average of only 0.5 weeks of the year. The budesonide group displayed greater improvement in pre-bronchodilator FEV₁ (+4.02% ± 1.20%; zafirlukast, –1.06% ± 1.00%; “intermittent only,” +0.66% ± 1.09%; p = 0.005) but not in post-bronchodilator FEV₁ (p > 0.25). Budesonide treatment was associated with improvements in questionnaire scores for asthma control and symptom-free days but not for quality of life. The criteria for mild persistent asthma may define a condition so mild that patients instructed in an action plan may decide whether to take daily anti-inflammatory therapy on the basis of their assessment of the importance of their symptomatic improvements. The major publication appeared in NEJM:

Boushey HA, Sorkness CA, King TS, Sullivan SD, Fahy JV, Lazarus SC, Chinchilli VM, Craig TJ, DiMango EA, Deykin A, Fagan JK, Fish JE, Ford JG, Kraft M, Kunselman SJ, Lemanske RF, Jr, Leone FT, Martin RJ, Mauger EA, Pesola GR, Peters SP, Rollings NJ, Szefler SJ, Wechsler ME, Israel EI. Regular vs. intermittent controller therapy for mild persistent asthma. New England Journal of Medicine 2005; 352:1519-1528.